Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma
Abstract Signet Ring Cell Carcinoma (SRCC) is a rare and highly malignant form of adenocarcinoma with increasing incidence and poor prognosis due to late diagnosis and limited treatment options. We employed Deep Visual Proteomics (DVP), which combines AI-directed cell segmentation and classification...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00819-7 |
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| author | Sonja Kabatnik Xiang Zheng Georgios Pappas Sophia Steigerwald Matthew P. Padula Matthias Mann |
| author_facet | Sonja Kabatnik Xiang Zheng Georgios Pappas Sophia Steigerwald Matthew P. Padula Matthias Mann |
| author_sort | Sonja Kabatnik |
| collection | DOAJ |
| description | Abstract Signet Ring Cell Carcinoma (SRCC) is a rare and highly malignant form of adenocarcinoma with increasing incidence and poor prognosis due to late diagnosis and limited treatment options. We employed Deep Visual Proteomics (DVP), which combines AI-directed cell segmentation and classification with laser microdissection and ultra-high sensitivity mass spectrometry, for cell-type-specific proteomic analysis of SRCC across the bladder, prostate, seminal vesicle, and a lymph node of a single patient. DVP identified significant alterations in DNA damage response (DDR) proteins, particularly within the ATR and mismatch repair (MMR) pathways, indicating replication stress as a crucial factor in SRCC mutagenicity. Additionally, we observed substantial enrichment of immune-related proteins, reflecting high levels of cytotoxic T lymphocyte infiltration and elevated PD-1 expression. These findings suggest that pembrolizumab immunotherapy may be more effective than conventional chemotherapy for this patient. Our results provide novel insights into the proteomic landscape of SRCC, identify potential targets, and open up for personalized therapeutic strategies in managing SRCC. |
| format | Article |
| id | doaj-art-ba95f67cc25e4875a804312a6371f605 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-ba95f67cc25e4875a804312a6371f6052025-02-09T12:09:26ZengNature Portfolionpj Precision Oncology2397-768X2025-02-019111310.1038/s41698-025-00819-7Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinomaSonja Kabatnik0Xiang Zheng1Georgios Pappas2Sophia Steigerwald3Matthew P. Padula4Matthias Mann5Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of CopenhagenNovo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of CopenhagenNovo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of CopenhagenDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistrySchool of Life Sciences and Proteomics Core Facility, Faculty of Science, University of Technology SydneyNovo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of CopenhagenAbstract Signet Ring Cell Carcinoma (SRCC) is a rare and highly malignant form of adenocarcinoma with increasing incidence and poor prognosis due to late diagnosis and limited treatment options. We employed Deep Visual Proteomics (DVP), which combines AI-directed cell segmentation and classification with laser microdissection and ultra-high sensitivity mass spectrometry, for cell-type-specific proteomic analysis of SRCC across the bladder, prostate, seminal vesicle, and a lymph node of a single patient. DVP identified significant alterations in DNA damage response (DDR) proteins, particularly within the ATR and mismatch repair (MMR) pathways, indicating replication stress as a crucial factor in SRCC mutagenicity. Additionally, we observed substantial enrichment of immune-related proteins, reflecting high levels of cytotoxic T lymphocyte infiltration and elevated PD-1 expression. These findings suggest that pembrolizumab immunotherapy may be more effective than conventional chemotherapy for this patient. Our results provide novel insights into the proteomic landscape of SRCC, identify potential targets, and open up for personalized therapeutic strategies in managing SRCC.https://doi.org/10.1038/s41698-025-00819-7 |
| spellingShingle | Sonja Kabatnik Xiang Zheng Georgios Pappas Sophia Steigerwald Matthew P. Padula Matthias Mann Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma npj Precision Oncology |
| title | Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma |
| title_full | Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma |
| title_fullStr | Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma |
| title_full_unstemmed | Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma |
| title_short | Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma |
| title_sort | deep visual proteomics reveals dna replication stress as a hallmark of signet ring cell carcinoma |
| url | https://doi.org/10.1038/s41698-025-00819-7 |
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